Evidence for the Role of B Cells and Immunoglobulins in the Pathogenesis of Multiple Sclerosis

The pathogenesis of multiple sclerosis (MS) remains elusive. Recent reports advocate greater involvement of B cells and immunoglobulins in the initiation and propagation of MS lesions at different stages of their ontogeny. The key role of B cells and immunoglobulins in pathogenesis was initially identified by studies in which patients whose fulminant attacks of demyelination did not respond to steroids experienced remarkable functional improvement following plasma exchange. The positive response to Rituximab in Phase II clinical trials of relapsing-remitting MS confirms the role of B cells. The critical question is how B cells contribute to MS. In this paper, we discuss both the deleterious and the beneficial roles of B cells and immunoglobulins in MS lesions. We provide alternative hypotheses to explain both damaging and protective antibody responses

Alternation of Glycocalyx in Critical Illness and during Major Surgery and Approaches for Glycocalyx Protection

Úvod: Glykokalyx představuje ochranný buněčný obal na sacharidové bázi. Buňce slouží jako komunikační médium s vnějším prostředí. Glykokalyx se vyskytuje též na apikálním povrchu cév, kde se nazývá endoteliální glykokalyx (EG). Výzkumy z posledních let deklarují jeho centrální roli ve fyziologii a patofyziologii mikrocirkulace. O stavu EG u pacientů v kritických stavech a během velkých chirurgických výkonů je dosud známo velmi málo a stále se vyvíjejí nové metody pro studium této komplexní struktury. Cíle: Cílem disertační práce bylo zhodnotit současnou úroveň znalostí o EG a metody jeho výzkumu. Popsat stav EG v experimentu na praseti domácím během náhlé zástavy oběhu (NZO) a na králíkovi během navozené hypernatrémie. Popsat stav EG u pacientů v perioperačním období při použití rozdílné anesteziologické techniky, dynamiku změny EG u pacientů v intenzivní péči, odezvu EG na tekutinovou výzvu 500 ml fyziologického roztoku (F 1/1) u zdravých dobrovolníků, změnu EG po podání tukové emulze u pacientů v intenzivní péči, kvalitu EG u pacientů s poruchou metabolizmu tuků (dyslipidémie a domácí dlouhodobá parenterální výživa) a kvalitu EG u zdravých dobrovolníků. Práce měla dále za cíl identifikovat ochranné látky a postupy pro EG a nastínit potenciální směr dalšího výzkumu. Metodika: EG byl studován jak v...Background: Glycocalyx represents a protective cellular coat on a sugar basis. It serves as a communication medium with outside environment. Glykokalyx also covers the inner apical surface of endothelial cells where it is called the endothelial glycocalyx (EG). Research from last decade declare its pivotal role in physiology and pathophysiology of microcirculation. EG is prone to be damaged in critical conditions but there are more questions than what we actually know about this complex structure. Also, there are new methods being developed for more precise description of EG condition. The aim: The aim of this thesis is to evaluate the level of contemporary evidence about EG and to evaluate methods of its assessment. To describe the condition of EG in experimental model of cardiac arrest (CA) in pig and in experimental model of iatrogenic hypernatremia in rabbit. To describe the influence of different types of anesthesia on EG in patients in perioperative care. To describe the dynamic changes of EG in patients in critical care. To evaluate response of EG to fluid challenge of 500 ml of normal saline in healthy volunteers and the response of EG to administration of lipid emulsion in patients in critical care. To describe the condition of EG in patients with dyslipidemia, with long term home parenteral...Chirurgická klinikaDepartment of SurgeryFaculty of Medicine in Hradec KrálovéLékařská fakulta v Hradci Králov

Alternation of Glycocalyx in Critical Illness and during Major Surgery and Approaches for Glycocalyx Protection

Background: Glycocalyx represents a protective cellular coat on a sugar basis. It serves as a communication medium with outside environment. Glykokalyx also covers the inner apical surface of endothelial cells where it is called the endothelial glycocalyx (EG). Research from last decade declare its pivotal role in physiology and pathophysiology of microcirculation. EG is prone to be damaged in critical conditions but there are more questions than what we actually know about this complex structure. Also, there are new methods being developed for more precise description of EG condition. The aim: The aim of this thesis is to evaluate the level of contemporary evidence about EG and to evaluate methods of its assessment. To describe the condition of EG in experimental model of cardiac arrest (CA) in pig and in experimental model of iatrogenic hypernatremia in rabbit. To describe the influence of different types of anesthesia on EG in patients in perioperative care. To describe the dynamic changes of EG in patients in critical care. To evaluate response of EG to fluid challenge of 500 ml of normal saline in healthy volunteers and the response of EG to administration of lipid emulsion in patients in critical care. To describe the condition of EG in patients with dyslipidemia, with long term home parenteral..

Neuraxial anesthesia is less harmful to the endothelial glycocalyx during elective joint surgery compared to general anesthesia

BACKGROUND: Damage of the endothelial glycocalyx (EG) has been described during surgery, but the effect of different anesthesia techniques remains unknown. Perfused boundary region (PBR) evaluated by side-stream dark field (SDF) imaging of the sublingual microcirculation enables in vivo EG assessment. PBR values are inversely related to the EG thickness. OBJECTIVE: The aim of the observational study was to evaluate the changes of PBR in patients undergoing elective joint surgery under general (GA) vs. neuraxial anesthesia (NA). Our hypothesis was that PBR will be lower in patients in NA. METHODS: Sixty consecutive patients (ASA 1-3) undergoing elective total knee or hip replacement under GA or NA were included in this prospective observational cohort study. PBR in the sublingual microcirculation was recorded in each patient using SDF at two time points - before surgery and 2 hours after surgery. RESULTS: Before surgery, there was no significant difference in baseline PBR between groups (NA: 1.95 mu m (+/- 0.24); GA: 2.02 mu m (+/- 0.26); p = 0.098). Postoperatively (2 hours after surgery) PBR was significantly increased in both groups with respect to baseline values (NA: 2.09 mu m (+/- 0.19), GA: 2.20 mu m (+/- 0.25); p <0.001). In the GA group, postoperative PBR values were significantly higher than in the NA group (p = 0.006). CONCLUSION: Joint surgery led to significant increases of PBR. Patients in the GA group had significantly higher PBR values 2 hours after surgery compared to NA group. This might implicate that NA is associated with less EG damage then GA in elective hip/knee surgery